Inadvertent potential risk of neoadjuvant chemotherapy in cervical cancer

Randomized clinical trials comparing neoadjuvant chemotherapy (NAC) followed by surgery with initial surgery in cervical cancer reported conflicting results. We provided a hypothesis explaining the different outcomes between trials. NAC was reported to make a lymph node metastasis smaller. Smaller tumors are hard to detect and potentially undetected at pathologic examination. Undetected metastasis would lead to an erroneous exclusion of high-risk patients from adjuvant therapy. An erroneous exclusion would lead to a recurrence. This harmful concealing effect of NAC could negate the potentially beneficial effect of NAC and the conflicting results of trials could be the result of the balance between harmful and beneficial effect of NAC. Because the concealing effect of NAC can be reversed by adjuvant therapy, trials comparing NAC followed by surgery with initial surgery in which all patients in both arms received adjuvant therapy reported positive result. However, in a trial in which only patients with lymph node or parametrial involvements received adjuvant therapy, the concealing effect was not reversed by adjuvant therapy and reported negative result. Our empirical data showed that patients who underwent NAC followed by surgery and were classified as low-risk based on pathologic parameters had unexpectedly high recurrence rate. To evaluate our hypothesis, a trial comparing a conventional pathologic examination with a more sophisticated examination such as ultrastaging in patients with cervical cancer who received NAC followed by surgery would be necessary. If our hypothesis is proven, trials considering the concealing effect of NAC should be performed to accurately evaluate the role of NAC in cervical cancer.